On December 22, 2015 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported the enrollment of the first patient in its Phase 1 trial of LOXO-101 in pediatric patients with advanced solid or primary central nervous system (CNS) tumors (Press release, Loxo Oncology, DEC 22, 2015, View Source [SID:1234508625]). LOXO-101 is the only selective inhibitor of the tropomyosin receptor kinase (TRK) protein family in clinical development. Schedule your 30 min Free 1stOncology Demo! "Given the promising early efficacy and tolerability results we have seen in adults with TRK fusion cancers, we are excited to explore the potential of LOXO-101 in children and adolescents with cancer," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "The TRK pathway has been implicated in many pediatric cancers, and this trial is an important step toward understanding LOXO-101 in these settings."
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The Phase 1 clinical trial is a multicenter, open-label trial in pediatric patients with advanced solid or primary CNS tumors. Loxo Oncology plans to open as many as 15 clinical sites in the U.S. In the dose-escalation phase, LOXO 101 will be administered orally twice daily, with the initial starting dose level intended to match the pharmacokinetic exposures of the 100 mg twice daily dose that is currently being employed in the LOXO-101 Phase 2 basket trial in adult patients. The actual dose for each patient will depend on patient body size and age. The trial will also utilize a liquid formulation of LOXO-101 designed specifically for pediatric patients unable to swallow capsules. The primary endpoint of the trial is to explore the safety of LOXO-101. Secondary endpoints include the characterization of pharmacokinetic properties, the identification of the maximum tolerated dose and/or the Phase 2 dose, a description of antitumor activity, and a description of pain and health related quality of life impact.
In order to meet the criteria for enrollment, patients must be between one year of age and 21 years of age with a locally advanced or metastatic solid tumor or primary CNS tumor that has progressed, or was nonresponsive to available therapies, and for which no standard or available curative therapy exists. Patients at least one month old are eligible for enrollment if they have a diagnosis of infantile/congenital fibrosarcoma, with a documented NTRK fusion that has progressed, or was nonresponsive to available therapies, and for whom no standard or available curative therapy exists.
Additional patient cohorts may be enrolled in an expansion phase of the Phase 1 trial to better characterize safety and efficacy in patients with specific abnormalities in the NTRK genes or proteins.
The TRK pathway plays an important role in many pediatric cancers. TRK gene fusions have been described in pediatric tumor types such as infantile/congenital fibrosarcoma, congenital mesoblastic nephroma, secretory breast carcinoma, pontine glioma, and may occur at increased frequency in younger patients with other tumor types, according to proprietary Loxo Oncology analyses. TRK signaling may also play a role in neuroblastoma.
LOXO-101 has shown objective clinical responses in adult patients with tumors harboring TRK gene fusions in a Phase 1 trial. LOXO-101 is also being evaluated in a global Phase 2 multi-center basket trial in adult patients with solid tumors that harbor TRK gene fusions.
About LOXO-101
LOXO-101 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an ongoing Phase 1 clinical trial, LOXO-101 has demonstrated encouraging preliminary efficacy. LOXO-101 is also being evaluated in a global Phase 2 multi-center basket trial in patients with solid tumors that harbor TRK gene fusions, and a Phase 1 dose escalation trial in pediatric cancer patients. For additional information about both the LOXO-101 clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123.
Author: [email protected]
OPKO’s GeneDx Study of More Than 10,000 Individuals Tested with Multigene NGS Hereditary Cancer Panel Reveals New Risks
On December 21, 2015 OPKO Health, Inc. (NYSE: OPK) through its subsidiary GeneDx, reported results from the largest published study to date of patients who received hereditary genetic testing with Next Generation Sequencing (NGS) cancer panels (Press release, Opko Health, DEC 21, 2015, View Source [SID:1234508623]). The study, "Pathogenic and Likely Pathogenic Variant Prevalence among the First 10,000 Patients Referred for Next Generation Cancer Panel Testing," was published in the December 2015 issue of Genetics in Medicine. GeneDx’s analysis of the data generated from the first 10,030 patients highlights the clinical utility of testing for multiple cancer genes to identify variants that would not have been identified through previously used testing methods. The patients, who were referred for testing between August, 2013 and October, 2014, underwent genetic testing for panels of genes associated with hereditary cancer.
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While many patients were found to carry pathogenic or likely pathogenic variants in well-established, high-risk cancer genes, approximately half of the pathogenic variants identified were in genes with moderate risk and in recently identified cancer genes. Notably, among women with breast cancer, 50% of positive findings were in genes other than BRCA1 or BRCA2. Additionally, several individuals had pathogenic variants in high-risk genes that were somewhat unexpected, so clinical presentation alone might not have prompted testing for these genes.
"We believe that molecular diagnostic testing for panels containing multiple genes are significantly more accurate in determine the heritable factors which increase the risk of cancer, and may permit more tailored treatment for cancer patients and screening for their family members," said Sherri Bale, PhD, FACMG, Co-Founder and Managing Director of GeneDx. "Our experience, based on a large database of patients, demonstrates that multi-gene panels have the potential to identify pathogenic variants in genes that would not typically have been tested and most likely would have been missed. This study provides important empirical data for clinical decision-making when choosing between single genes and NGS cancer panel testing for a variety of cancers."
Foundation Medicine Announces National Agreement with UnitedHealthcare for FoundationOne® in Metastatic Non-Small Cell Lung Cancer
On December 21, 2015 Foundation Medicine, Inc. (NASDAQ:FMI) reported that it has signed a national agreement for FoundationOne, a comprehensive genomic profiling assay for solid tumors, with UnitedHealthcare, one of the nation’s largest private payers (Press release, Foundation Medicine, DEC 21, 2015, View Source [SID:1234508618]). The Agreement, which became effective December 15, 2015, covers FoundationOne for patients with metastatic stage IV non-small cell lung cancer (NSCLC). In the United States, approximately 50 percent of patients with NSCLC have metastatic disease at the time of diagnosis.1
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FoundationOne is a comprehensive genomic profile that enables physicians to make treatment decisions for patients with cancer by identifying the molecular growth drivers of their cancers and by helping oncologists match the identified drivers with relevant targeted therapeutic options. Requiring only a small amount of tumor tissue, FoundationOne interrogates the entire coding sequence of 315 cancer-related genes plus select introns from 28 genes that are known to be altered in solid tumors.
"UnitedHealthcare’s coverage decision is a critical first step towards ensuring that comprehensive genomic profiling becomes standard-of-care treatment for patients with metastatic disease," said Bonnie J. Addario, lung cancer survivor, and founder of the Bonnie J. Addario Lung Cancer Foundation and the Addario Lung Cancer Medical Institute. "Lack of reimbursement for comprehensive genomic profiling tests, like FoundationOne, continues to be one of the major barriers impeding patient access to potentially life-extending therapies for which the patient is a molecular match."
"This national coverage agreement with UnitedHealthcare is an important step towards broader reimbursement for Foundation Medicine, and importantly, it’s a significant advance for patients with metastatic NSCLC," said Michael Pellini, M.D., chief executive officer for Foundation Medicine. "Studies demonstrate that improved clinical outcomes are achieved by matching patients to targeted therapies based on the unique genomic alterations contributing to the disease. We look forward to building upon our relationship with UnitedHealthcare and other national insurers as we continue to demonstrate clinical and economic evidence supporting coverage and payment for FoundationOne in additional cancer types."
8-K – Current report
On December 21, 2015 Array BioPharma Inc. (NASDAQ: ARRY) reported the closing of its definitive agreement with Pierre Fabre following approval of the agreement by the European Commission on Competition (ECC) (Filing, 8-K, Array BioPharma, DEC 21, 2015, View Source [SID:1234508616]). The definitive agreement, announced on November 16, 2015, relates to globally developing and commercializing Array’s late-stage novel oncology products, binimetinib and encorafenib. Binimetinib, a MEK inhibitor, and encorafenib, a BRAF inhibitor, are currently advancing in three, global Phase 3 trials for melanoma and ovarian cancer.
About the Array / Pierre Fabre Agreement
Under the terms of the agreement, Array will receive an upfront payment of $30 million and retains exclusive commercialization rights for binimetinib and encorafenib in the United States, Canada, Japan, Korea and Israel. Pierre Fabre will have exclusive rights to commercialize both products in all other countries, including Europe, Asia and Latin America. Array is entitled to receive up to $425 million if certain development and commercialization milestones are achieved, and is eligible for robust, tiered double-digit royalties. Array and Pierre Fabre have agreed to split future development costs on a 60:40 basis (Array:Pierre Fabre) with initial funding committed for new clinical trials in colorectal cancer and melanoma. All ongoing binimetinib and encorafenib clinical trials remain substantially funded through completion by Novartis.
About Binimetinib and Encorafenib
RAF and MEK are key protein kinases in the RAS/RAF/MEK/ERK pathway. Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, migration, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, such as non-small cell lung cancer, melanoma, colorectal, ovarian and thyroid cancers. Binimetinib is a small molecule MEK inhibitor and encorafenib is a small molecule BRAF inhibitor, both of which target key enzymes in this pathway. Three Phase 3 trials in advanced cancer patients continue to advance: NRAS-mutant melanoma (NEMO, with binimetinib), low-grade serous ovarian cancer (MILO, with binimetinib) and BRAF-mutant melanoma (COLUMBUS, with binimetinib and encorafenib). Array announced on December 16, 2015 that NEMO met its primary endpoint of improving progression-free survival compared with dacarbazine treatment. Array plans to submit binimetinib to regulatory authorities for marketing approval in NRAS-mutant melanoma during the first half of 2016. Array also projects a regulatory filing of binimetinib in combination with encorafenib in BRAF melanoma in 2016.
About Pierre Fabre and Pierre Fabre Oncology
Pierre Fabre is a French privately-owned health and beauty care company created in 1961 by Mr. Pierre Fabre. In 2014, global sales reached €2.1 billion across 130 countries. The company is structured around two divisions: Pharmaceuticals (Prescription drugs, Consumer Health Care) and Dermo-cosmetics (including the European and Asian market-leader Eau Thermale Avene brand). Pierre Fabre employs some 10,000 people worldwide and owns subsidiary in 43 countries. In 2014, the company allocated 17 percent of its pharmaceuticals sales to R&D with a focus on 4 therapeutic areas: oncology, dermatology, CNS and consumer health care.
Pierre Fabre Oncology, a business unit of the Pierre Fabre company, is supported by over 1,000 employees with a strong focus on European markets. In 2014, worldwide annual sales of Pierre Fabre Oncology products surpassed $200 million on the strength of the Oral Navelbine, Javlor and Busilvex brands. In addition, Pierre Fabre has a significant commitment and track record in pharmaceutical R&D, developing products for patients afflicted with lung, breast and other solid tumors and hematological cancers.
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Aduro Biotech Announces Initiation of Phase 1 Study of ADU-741 for the Treatment of Prostate Cancer
On December 21, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that the first patient in the Phase 1 study of ADU-741 (also known as JNJ-64041809), a LADD immunotherapy product candidate for the treatment of prostate cancer, has been dosed. Janssen Biotech, Inc., is Aduro’s license partner for ADU-741 (Press release, Aduro BioTech, DEC 21, 2015, View Source [SID:1234508624]). Janssen is conducting the study. Schedule your 30 min Free 1stOncology Demo! "Janssen has deep expertise in the development of therapeutics for prostate cancer and we are extremely pleased with the rapid advancement of ADU-741 into clinical trials," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "ADU-741 represents a highly-specific, multifaceted approach to stimulate the immune system to fight cancer and we believe it may offer a new and unique treatment alternative to improve the outcome of men suffering from metastatic castration-resistant prostate cancer. We are particularly excited about ADU-741, which represents a significant advancement of our LADD technology and utilizes our proprietary methods to express multiple antigens that are relevant to prostate cancer. By engaging in productive agreements with partners like Janssen, Novartis and Incyte, we expand the reach of our novel immuno-oncology platform and offset the development costs of our internal therapies, all of which we pursue for the ultimate goal of bringing new treatments to patients in need."
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The Phase 1 study will enroll approximately 40 patients with metastatic castration-resistant prostate cancer. The initial dose escalation portion of the trial, with two dose levels of ADU-741, will evaluate safety and immunogenicity. The trial will then expand to further characterize safety and preliminary immunological and clinical activity. Additional information may be found at clinicaltrials.gov, using identifier NCT02625857.
About LADD
LADD is Aduro’s proprietary platform of live-attenuated double-deleted Listeria monocytogenes strains that have been engineered to induce a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity. The LADD technology has been applied to several novel compounds in clinical and preclinical testing including CRS-207 (pancreatic cancer, mesothelioma and ovarian/fallopian/peritoneal cancer (collaboration with Incyte Corporation to be tested in combination with epacadostat)), ADU-623 (brain cancer), ADU-214 (lung cancer, licensed to Janssen Biotech, Inc.) and ADU-741 (prostate cancer, licensed to Janssen Biotech, Inc.).